Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity

Song, Deyong; Liu, Xiu; Dong, Chuangchuang; Wang, Qiaoping; Sha, Chunjie; Liu, Chuan; Zong, Ning; Han, Jing; Liu, Hong; Zong, Mengqi; Zhao, Yanyan; Li, Ying; Liu, Guangsheng; Shao, Xin; Dou, Changlin

doi:10.1038/s41598-021-02449-y

Cited by 5 publications

(9 citation statements)

References 27 publications

(25 reference statements)

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“…IL2RA can influence the activity of Treg cells to assist in the regulation of immunological tolerance 69 . Targeting and eliminating Treg cells through the use of CD25 antibodies have been recognized as a key mechanism for tumor inhibition and the elimination of immunosuppression 70 . Overall, our results suggest that lower airway dysbiosis in lung cancer is associated with distinct cytokine profiles and microbial compositions.…”

Section: Discussionmentioning

confidence: 72%

Dysbiosis of lower respiratory tract microbiome are associated with proinflammatory states in non‐small cell lung cancer patients

Li,

Rao,

Zhu

et al. 2023

Thoracic Cancer

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BackgroundThe lung has a sophisticated microbiome, and respiratory illnesses are greatly influenced by the lung microbiota. Despite the fact that numerous studies have shown that lung cancer patients have a dysbiosis as compared to healthy people, more research is needed to explore the association between the microbiota dysbiosis and immune profile within the tumor microenvironment (TME).MethodsIn this study, we performed metagenomic sequencing of tumor and normal tissues from 61 non‐small cell lung cancer (NSCLC) patients and six patients with other lung diseases. In order to characterize the impact of the microbes in TME, the cytokine concentrations of 24 lung tumor and normal tissues were detected using a multiple cytokine panel.ResultsOur results showed that tumors had lower microbiota diversity than the paired normal tissues, and the microbiota of NSCLC was enriched in Proteobacteria, Firmicutes, and Actinobacteria. In addition, proinflammatory cytokines such as IL‐8, MIF, TNF‐ α, and so on, were significantly upregulated in tumor tissues.ConclusionWe discovered a subset of bacteria linked to host inflammatory signaling pathways and, more precisely, to particular immune cells. We determined that lower airway microbiome dysbiosis may be linked to the disruption of the equilibrium of the immune system causing lung inflammation. The spread of lung cancer may be linked to specific bacteria.

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Section: Discussionmentioning

confidence: 72%

Dysbiosis of lower respiratory tract microbiome are associated with proinflammatory states in non‐small cell lung cancer patients

Li,

Rao,

Zhu

et al. 2023

Thoracic Cancer

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“…It relieves immune suppression in the TME. BA1106 is expected to compensate for the shortcomings of current anti‐PD‐1 therapies 91 …”

Section: Drugs Targeting Cd25mentioning

confidence: 99%

“…If the follow‐up clinical trial of IL‐2 non‐blocking anti‐CD25 antibodies gains success, it will bring a new type of immunotherapy to patients with increased Tregs frequency in the TME 90‐93 …”

Section: Drugs Targeting Cd25mentioning

confidence: 99%

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CD25: A potential tumor therapeutic target

Peng

Tao

Zhang

et al. 2022

Intl Journal of Cancer

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CD25 is the alpha‐chain of the heterotrimer IL‐2 receptor. CD25 is expressed on the surface of both immune and non‐immune cells with different frequencies. For cancers, CD25 is expressed at high levels in many types of hematological malignancies, but at low levels in most solid tumors. CD25 is also highly expressed in activated circulating immune cells and regulatory T cells (Tregs). Infiltration of Tregs in the tumor microenvironment can lead to an imbalanced ratio of effector T cells (Teffs) and Tregs, which is associated with the progression of cancers. A rescued Teff/Treg cell ratio indicates an efficient anti‐tumor response to immunotherapy. CD25 as a potential target for the depletion of Tregs is critical in developing new immunotherapeutic strategies. Few articles have summarized the relationships between CD25 and tumors, or the recent progress of drugs targeting CD25. In this paper, we will discuss the structures of IL‐2 and IL‐2R, the biological function of CD25 and its important role in tumor therapy. In addition, the latest research on drugs targeting CD25 has been summarized, providing guidance for future drug development.

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“…This suggests that non‐IL‐2‐blocking anti‐CD25 antibodies could preferentially deplete Tregs without suppressing Teff activation, potentially improving tumor immunity. Currently, two non‐IL‐2‐blocking anti‐CD25 antibodies RG6292 and BA1106, developed by Roche and Boan Biotech respectively, have been reported with enhanced tumor immunity 37,38 . These results indicated that the different epitopes on CD25 antigen may exert significant impact on immune regulation function of anti‐CD25 antibodies.…”

Section: Introductionmentioning

confidence: 97%

Non‐IL‐2‐blocking anti‐CD25 antibody inhibits tumor growth by depleting Tregs and has synergistic effects with anti‐CTLA‐4 therapy

Peng,

Fu,

Liu

et al. 2024

Intl Journal of Cancer

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CD25, also known as the interleukin‐2 receptor α chain (IL‐2Rα), is highly expressed on regulatory T cells (Tregs), but relatively lower on effector T cells (Teffs). This makes it a potential target for Treg depletion, which can be used in tumor immunotherapy. However, marketed anti‐CD25 antibodies (Basiliximab and Daclizumab) were originally developed as immunosuppressive drugs to prevent graft rejection, because these antibodies can block IL‐2 binding to CD25 on Teffs, which in turn destroys the function of Teffs. Recent studies have shown that non‐IL‐2‐blocking anti‐CD25 antibodies have displayed exciting antitumor effects. Here, we screened out a non‐IL‐2‐blocking anti‐CD25 monoclonal antibody (mAb) 7B7 by hybridoma technology, and confirmed its antitumor activity via depleting Tregs in a CD25 humanized mouse model. Subsequently, we verified that the humanized 7B7, named as h7B7‐15S, has comparable activities to 7B7, and that its Treg depletion is further increased when combined with anti‐CTLA‐4, leading to enhanced remodeling of the tumor immune microenvironment. Moreover, our findings reveal that the Fab form of h7B7‐15S has the ability to deplete Tregs, independent of the Fc region. Taken together, our studies expand the application of anti‐CD25 in tumor immunotherapy and provide insight into the underlying mechanism.

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Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity

Cited by 5 publications

References 27 publications

Dysbiosis of lower respiratory tract microbiome are associated with proinflammatory states in non‐small cell lung cancer patients

Dysbiosis of lower respiratory tract microbiome are associated with proinflammatory states in non‐small cell lung cancer patients

CD25: A potential tumor therapeutic target

Non‐IL‐2‐blocking anti‐CD25 antibody inhibits tumor growth by depleting Tregs and has synergistic effects with anti‐CTLA‐4 therapy

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